Elevated LFTs Research Articles

Clinical predictors of significant findings on EUS for the evaluation of incidental common bile duct dilation

Although EUS is highly accurate for the evaluation of common bile duct (CBD) dilation, the yield of EUS in patients with incidental CBD dilation is unclear. Serial patients undergoing EUS for incidental, dilated CBD (per radiologist, minimum of >6mm objectively) from 2 academic medical centers without active pancreaticobiliary disease or significantly elevated liver function test results were evaluated. Multivariable logistic regression identified predictors of EUS with significant findings and a novel prediction model was derived from one center, internally validated with bootstrapping, and externally validated at the second center. Of 375 patients evaluated, 31 (8.3%) had significant findings, including 26 choledocholithiasis, 1 ampullary adenoma, and 1 pancreatic mass. Predictors of significant findings with EUS included age of≥70 years (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-10.0), non-biliary-type abdominal pain without chronic pain (OR, 6.1; 95% CI, 2.3-17.3), CBD diameter of≥15mm or≥17mm with cholecystectomy (OR, 6.9; 95% CI, 2.7-18.7), and prior ERCP (OR, 6.8; 95% CI, 2.1-22.5). A point-based novel clinical prediction model was created: age of≥70 years= 1, non-biliary-type abdominal pain without chronic pain= 2, prior ERCP= 2, and CBD dilation= 2. A score of<1 had 93% (development) and 100% (validation) sensitivity and predicted a<2% chance of having a significant finding in both cohorts while excluding the need for EUS in ∼30% of both cohorts. Conversely, a score of≥4 was >90% specific for the presence of significant pathology. Less than 10% of patients undergoing EUS for incidental CBD dilation had pathologic findings. This novel, externally validated, clinical prediction model may reduce low-yield, invasive evaluation in nearly one-third of patients.

Abstract 16717: Managing Myxedema Coma: A Challenging Case of Cardiogenic Shock Culminating in Orthotopic Heart Transplantation

Background: Myxedema coma (MC) is a rare manifestation of severe hypothyroidism often seen in elderly female patients. While the sequelae of MC can lead to multi-organ involvement and eventual failure, irreversible Heart Failure (HF) is rarely seen. This case culminated in orthotopic heart transplant (OHT) for definitive treatment. Case Presentation: A 23-year-old male presented with worsening RUQ abdominal pain for 2 weeks. In the ED, he had PEA arrest and with ROSC, he was admitted to the CCU for presumed cardiogenic shock, with labs remarkable for lactate 7.5 mmol/L, pro-BNP 6104 pg/mL, and markedly elevated serum creatinine and LFTs. The patient exhibited HF symptoms for 9 months before admission, manifesting as worsening LE edema, fatigue, and weight gain. He was also noted to have untreated hypothyroidism with repeat TSH of 857 μIU/mL on admission, indicating MC as a potential trigger for worsening HF. TTE revealed severe biventricular dysfunction with global hypokinesis and LVEF of 10-15%. Inotropic support was initiated with dobutamine, with RHC showing CVP 11 mmHg, RV 23/11 mmHg, PA 32/22 mmHg, PCWP 25 mmHg, and CI 2.3 LPM/m 2 . Subsequent deterioration in CI and MVO2 necessitated IABP placement and vasopressor support, and later rescue VA-ECMO with atrial septostomy, aiming for OHT. Endocrine evaluation confirmed primary hypothyroidism, and the patient received high-dose levothyroxine, T3, and stress-dosed steroids. While there have been instances where cardiac consequences of myxedema HF were reversed by thyroid administration, his significantly dilated left ventricular internal dimension at end diastole, as well as complications of ECMO (bleeding) expedited his transplant evaluation. OHT was successfully performed on hospital day 14. Continuous improvement in thyroid function studies was observed throughout the treatment course with levothyroxine therapy. Discussion: Worsening HF in the setting of MC, particularly in a male patient, is an uncommon presentation that requires prompt action. This patient required mechanical support as an eventual bridge to OHT with simultaneous treatment for hypothyroidism, illustrating the complexity of the case and the interventions necessary for a positive outcome in an uncommon clinical scenario.

FRI573 Liver Enzyme Elevation In A Patient With Grave’s Disease; Could This Be Due To Anti-thyroid Drug Therapy?

Abstract Disclosure: C.S. Park: None. J.L. Gilden: None. Introduction: Abnormal liver enzymes (LFTs) are often observed in patients with both hypothyroidism, as well as in 2.5% of patients with Grave’ s (GRAVES) Hyperthyroidism (HTH) treated with anti-thyroid medications (ATD). Furthermore, abnormal Liver function tests are reported within 6 months of untreated thyrotoxicosis in 39% of patients. The other common causes of abnormal LFTs in HTH are congestive hepatopathy with thyrotoxic heart failure, previous underlying liver disease, hypermetabolism of hepatocytes due to HTH with subsequent anoxia and free radical damage, hepatocyte degeneration due to glycogen and protein decomposition acceleration, and autoimmune-related liver injury. Case: A 52-year-old Mexican American female, with allergies, and recent COVID vaccine, was referred to the endocrine clinic for an unknown duration of GRAVES with unintentional weight loss and occasional tremors of three months duration, and some leg weakness, but denied other symptoms of hyperthyroidism, gastrointestinal disorders, or other autoimmune disorders. There was no known family history of HTH, or other autoimmune disorders. She presented after initiation of methimazole (MMI) 5 mg twice daily, prescribed by her primary care provider. VS BP 137/70 HR 94 BMI 25.32. Exam-slight tremor on outstretched arms, no ophthalmopathy, 35-40 gm thyromegaly, no onycholysis or pretibial myxedema. Labs: TSH &amp;lt;0.010 (0.27-4.20 mIU/mL); Free T4 1.84 (0.5-1.6 ng/dL); T3 Free 5.31 (2.52-4.34 pg/mL); TG AB 100 (0-4 IU/mL); Thyroid Peroxidase 1,425.00 (0.00-9.00 iu/Ml); TSI 27.10 (&amp;lt;=0.54 iu/l). LFT’s were elevated (AST 105, repeat 53, (13-39 U/L);ALT 272,repeat 150 (7-52U/L); Alkaline Phosphatase (AP) 305,repeat 290 (34-104 U/L); T.Bilirubin 0.4 (0.0-1.0 mg/dL)]. AP Bone 159 (0-55 U/L) AP liver 195 (0-94 U/L). ANA was positive with SCL-70 autoantibodies 5.0 (&amp;lt;1.0 AI). Thyroid US: slightly heterogenous thyroid gland of chronic thyroiditis. RUQ abdominal US-normal. MMI was stopped for 2 weeks, then restarted. 1 week later-TSH &amp;lt;0.10 uIu/mL, Free T4 1.79 ng/dL, Free T3 5.91 pg/mL and LFT’s improved over the next several weeks (AST 39 U/L; ALT 85 U/L; Alkaline Phosphatase 220 U/L. SCL-70 remained positive, and she remained asymptomatic. Conclusion: Although the etiology for LFT elevation is suggestive of MMI treatment, since it occurred with the initiation and titration of this therapy, this patient also had markedly elevated SCL-70, seen in 20% of patients with systemic sclerosis, which can also be associated with lupus erythematosus, and primary biliary cirrhosis. Furthermore, the elevation continued, even after MMI had been stopped and then when restarted, was lower. This case demonstrates that it is crucial to evaluate for other etiologies of elevated LFTS in any patient with HTH, and not just assume that it is due to GRAVES or ATD, and also to consider the possibility of other autoimmune conditions. Presentation: Friday, June 16, 2023

Real-world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study.

We conducted a retrospective multi-centre study to assess the real-world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs) including osteosarcoma (OST), Ewing sarcoma (EWS) and chondrosarcoma (CS)/extra-skeletal mesenchymal CS (ESMC). After regulatory approval, data from patients with recurrent BT (11 institutions) were extracted from CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database. Patient characteristics, treatment and outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. From July 2018 to May 2022, 66 patients received REGO or CABO; 39 OST, 18 EWS, 4 CS and 5 ESMC. Median age was 27.8 years (range 12-76); median starting dose was 60 mg for CABO (n = 37, range 40-60) and 120 mg for REGO (n = 29, range 40-160). Twenty-eight (42.4%) patients required dose reduction: hand-foot syndrome 7 (10.6%), nausea/vomiting 1 (1.5%), diarrhoea 1 (1.5%), 2 elevated LFTs (3%), elevated bilirubin 1 (1.5%) and mucositis 1 (1.5%). The median OS for patients with OST, EWS, CS and ESMC was 8.5 months (n = 39, 95% CI 7-13.1); 13.4 months (n = 18, 95% CI 3.4-27.2), 8.1 (n = 4, 95% CI 4.1-9.3) and 18.2 (n = 5, 95% CI (10.4-na), respectively. Median PFS for OST, EWS, CS and ECMS was 3.5 (n = 39, 95% CI 2.8-5), 3.9 (n = 18, 95% CI 2.1-5.9), 5.53 (n = 4. 95% CI 2.13-NA) and 11.4 (n = 5, 95% CI 1.83-14.7), respectively. Age, line of therapy, REGO versus CABO, or time from diagnosis to initiation of TKI were not associated with PFS on univariable analysis. Our real-world data show that TKIs have meaningful activity in recurrent BT with acceptable toxicities when started at modified dosing. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research.

Lack of IgA and IgA+ switched memory B cells are associated with bacterial translocation in CVID

BackgroundGut bacterial translocation (BT) is linked to immune activation and inflammatory manifestations in CVID, accompanied by evidence of intestinal barrier defect. Here, we investigated the demographic, immunologic and biochemical parameters associated with BT and gut barrier dysfunction in CVID. MethodsWe measured serum biomarkers of BT (bacterial 16S rDNA [bDNA], by qt-PCR) and intestinal barrier defects (intestinal fatty-acid binding protein [I-FABP], by ELISA) in 88 CVID and 17 healthy control (HC) subjects. B cell phenotypes (% class-switched memory B cells [SMB, CD19 +CD27+IgM-IgD-/CD19+] and % IgA+ SMB [CD19+CD27+IgA+/CD19+]) were enumerated by flow cytometry. Results88 CVID subjects aged 21–62 years were recruited (baseline median IgG 202 [IQR 105–357], IgA 7 [< 5–15], IgM 11 [5–28] mg/dL, and SMB 1% [0.15–2.36%]). Serum bDNA and I-FABP were significantly elevated in CVID vs. HC (P < 0.0001, P < 0.001, respectively). Amongst CVID subjects, serum bDNA correlated with I-FABP levels (Spearman r = 0.27, P = 0.029). Serum bDNA and I-FABP levels were not age-dependent in this adult cohort. There were no sex differences in bDNA levels, though higher I-FABP was observed in males (p = 0.02). Serum bDNA and I-FABP were significantly elevated regardless of overt clinical enteropathy, though those with enteropathy had higher median levels vs. those without.Regarding immunologic and biochemical parameters, high serum bDNA was inversely correlated with 1) %IgA+ SMB (Spearman r = –0.52, P = 0.019, n = 23), and 2) serum IgA (Spearman r = –0.34, P = 0.002). Additionally, bDNA was significantly higher in those with elevated LFTs (P = 0.03). A negative trend between bDNA and total SMB was also observed. Gut barrier defect, as probed by I-FABP, was significantly higher in CVID patients with 1) undetectable IgA (p = 0.03), 2) abnormal liver function tests (p = 0.03), and negatively correlated with 3) CD4+ T cell counts (R = –0.34, p = 0.015). Serum bDNA and I-FABP were not associated with baseline IgG, IgM, or other B/T subsets examined. ConclusionLack of IgA and IgA+SMB are main immunologic parameters associated with BT in CVID, while abnormal LFTs may be an indirect indicator for BT and gut barrier defects. Our data suggest a role of IgA+ B cells/IgA as biological determinants of BT, and a link between BT and liver pathologies in CVID.

Abstract OT2-01-06: Phase II trial of palbociclib plus endocrine therapy followed by combination of pembrolizumab, palbociclib and endocrine therapy in patients with hormone receptor positive metastatic breast cancer

Abstract Background: The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is standard-of-care for patients with hormone receptor positive (HR+) HER2- metastatic breast cancer (MBC). Immune modulatory effects of CDK4/6i are well documented preclinically but poorly understood in the clinical setting. Our previous study combining letrozole, palbociclib and pembrolizumab in patients with HR+ MBC (NCT02778685) showed a promising complete response rate of 31%. Dynamic changes in peripheral blood mononuclear cell (PBMC) subpopulations indicated that palbociclib may increase CD8+ TEMRA (terminally differentiated effector memory cells) and CD4+ TEM (effector memory cells) and enable immune activation. The current cohort 3 was designed to study the immune modulatory effect of palbociclib as an immune-priming agent with a biomarker enriched design. Methods: Women with ECOG 0-1, HR+ HER2- MBC, RECIST 1.1 measurable disease, no prior therapy for MBC were enrolled. Patients with endocrine therapy, including aromatase inhibitor +/- ovarian suppression or fulvestrant, were eligible. A palbociclib + ET lead-in design was used, starting on day -28 followed by combination therapy with pembrolizumab added on C1D1. Peripheral blood and tumor biopsy at baseline and on-treatment were collected to allow in-depth analysis of biomarkers predicting response to the combination. The primary endpoint was to evaluate if the palbociclib potentiated immune responses as a “priming” agent through PBMC analysis and on treatment tumor biopsy. Secondary endpoints included other immune cell subsets and changes that follow the combination with pembrolizumab. With 25 patients, assuming a standard deviation of 0.51 in the relative change in classic monocytes in PBMCs, there is 90% power to detect a relative change of log(C1D1/baseline) of 34.5% with a type I error (two-sided) of 0.05. Results: Between August 2020 and April 2022, 16 patients were enrolled in cohort 3. Currently 11 patients have adverse event (AEs) and 16 patients have response data. Median age was 57 years (39-72). 8/11 (73%) were non-Hispanic white, 1/11 (9%) Hispanic, 1/11 (9%) Asian, and 1/11 (9%) African American. 87% patients had grade 3 AEs, and 30% had grade 4 AEs. Grade 3 AEs were 9/11 (82%) neutropenia, 5/11 (45%) leukopenia, 1/11 (9%) elevated LFTs, and 1/11 (9%) each lymphopenia, hot flashes, febrile neutropenia, and pneumonitis. Grade 4 AEs were 1/11 (9%) lymphopenia. 8/16 (50%) patients achieved a partial response (PR), 5/16 (31%) had stable disease (SD), and 1/16 (6%) had progression of disease (PD) by RECIST 1.1. Additionally, 2/16 (13%) patients were too early to determine best overall response. Response rate (CR+PR) was 50%. PBMCs and tumor microenvironment profiling are ongoing. Conclusion: The combination of palbociclib, pembrolizumab and ET is well tolerated, and a response rate of 50% was identified in HR+ MBC patients who received this combination as front-line therapy. Dynamic changes in peripheral blood mononuclear cells and tumor microenvironment profiling are ongoing. Citation Format: Yuan Yuan, Colt A. Egelston, Weihua Guo, Susan E. Yost, Paul H. Frankel, Christopher Ruel, Mireya Murga, Aileen Tang, Norma Martinez, Daniel Schmolze, Daphne Stewart, James Waisman, Kelly Yap, Joanne Mortimer, Niki Tank. Phase II trial of palbociclib plus endocrine therapy followed by combination of pembrolizumab, palbociclib and endocrine therapy in patients with hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-06.

ODP322 Impact of Mifepristone on Liver Function and Resolution of Liver Steatosis in Patients with Cushing Syndrome – A Case Study

Abstract Background Hypercortisolism is a recognized cause of non-alcoholic fatty liver disease (NAFLD). Mifepristone (Korlym®, Corcept Therapeutics), a glucocorticoid receptor (GR) antagonist, is FDA-approved for the treatment of hyperglycemia in patients with endogenous Cushing syndrome (CS). Mifepristone has also shown beneficial effects in preclinical models of fatty liver disease, including reduced liver injury, improved insulin sensitivity, and increased plasma adiponectin concentrations. Here, we report the case of a patient with CS and liver steatosis who was treated intermittently with mifepristone. Clinical Case A 36-year-old woman with CS associated with uncontrolled type 2 diabetes mellitus, obesity, major depressive disorder, hyperlipidemia, hypertension, and liver steatosis was intermittently treated with mifepristone for 3 years. Abdominal imaging was performed several times for abdominal pain. Before treatment with mifepristone was initiated, the patient had a body weight of 198 lbs, BMI of 32kg/m 2, HbA1c of 11.5%, and liver steatosis as noted on abdominal imaging with normal liver function tests (ALT: 40 U/L [normal: 6-42 U/L], AST: 30 U/L [normal: 8-36 U/L]). After 16 months, treatment with mifepristone was discontinued secondary to abnormal uterine bleeding. Imaging performed around the time of discontinuation showed resolution of liver steatosis, which was accompanied by significant reductions in LFTs to levels typically seen in healthy volunteers without liver steatosis (ALT: 10 U/L, AST: 17 U/L). The patient's HbA1c had decreased to 6.8%. Imaging performed 7months after mifepristone discontinuation showed recurrence of liver steatosis, LFTs had returned to pre-treatment values (ALT: 42 U/L, AST: 31U/L), and HbA1c had increased to 9.3%. The patient underwent hysterectomy and restarted mifepristone treatment. One year after resumption of mifepristone, imaging showed that liver steatosis had resolved once again, along with a similar reduction in LFTs as observed before (ALT: 16 U/L, AST: 12 U/L). Fourteen months after restart, mifepristone was discontinued again. Labs and imaging performed 10 months after discontinuation showed, as previously, recurrence of liver steatosis along with elevated LFTs (ALT: 100 U/L, AST: 56 U/L). Data from mifepristone's prospective pivotal study (SEISMIC, NCT00569582) of 50 patients with CS also showed a similar reduction in ALT throughout the study, which was reversed during the 6-week discontinuation follow-up phase of the study. This was followed by a repeat reduction when mifepristone was restarted in the extension study (NCT00936741). Conclusion These results suggest that mifepristone is effective in improving liver function and decreasing liver steatosis in patients with endogenous CS, a trend that is also accompanied by improvement in insulin resistance and glycemic control. Presentation: No date and time listed

S3669 Spotting the Deceiver: Metastatic Urothelial Carcinoma to the Liver Masquerading as a Well-Differentiated Neuroendocrine Tumor Histologically

Introduction: Metastatic urothelial carcinoma of the bladder is generally considered an aggressive disease. It has the potential to metastasize to lymph nodes, bones, lungs, liver, and peritoneum. The accurate diagnosis of metastatic urothelial carcinoma is challenging especially in the setting of histological mimickers. Without pathological expertise and additional immunohistochemistry, metastatic tumors could remain incorrectly diagnosed and delay therapeutic intervention. Case Description/Methods: Herein, we describe a 62-year-old man who presented with jaundice, elevated LFTs, diffuse abdominal pain, and early satiety. MRI of the abdomen revealed a hilar hyperintense mass involving the common bile duct, bilateral hepatic ducts causing narrowing, a 1.1 cm mass in segment 6, and hydroureteronephrosis with thickening of the renal pelvis. Discussion: Clinical differential diagnosis included cholangiocarcinoma and other tumors including a metastatic neuroendocrine tumor (NET). Microscopic evaluation of liver mass biopsy revealed insular growth pattern with monotonous epithelioid cells arranged in nests morphologically suggestive of well-differentiated neuroendocrine tumor (WDNET). However, neuroendocrine immunohistochemical stains, including synaptophysin, chromogranin, and CD56, were all negative, and the Ki-67 staining was 37%, higher than expected for a WDNET, (see Figure 1) prompting broadening of the differential. Following further workup, a diagnosis of metastatic urothelial carcinoma was confirmed by immunopositivity for immunohistochemical markers P40, and GATA3 (see Figure 1). Familiarity with tumors that are histologically identical is critical. Considering an appropriate differential diagnosis, and following a stepwise immunohistochemical approach will be crucial in spotting the mimickers and rendering appropriate management promptly.Figure 1.: Metastatic urothelial carcinoma, hematoxylin & eosin (A and B), and immunohistochemical markers (C-F).

S3467 Primary Duodenal Adenocarcinoma: A Rare Malignancy

Introduction: Primary duodenal adenocarcinoma (PDA) is extremely rare, representing 0.3 – 1% of all gastrointestinal malignancies. It poses a significant challenge to the physicians due to late non-specific symptoms that delays the diagnosis. Surgical resection is the only treatment option although PDA with distant or nodal metastasis have a very poor prognosis. Case Description/Methods: A 33-year-old male patient presented with epigastric abdominal pain, nausea, vomiting, lipase > 2000, elevated LFTs and hyperbilirubinemia, consistent with acute pancreatitis. CT abdomen and pelvis revealed an irregular mass in the second and third portion of the duodenum near ampulla, dilation of pancreatic and common bile duct along with multiple hepatic lesions, consistent with metastatic malignancy. EGD showed non bleeding duodenal ulcer along with enlarged lymph nodes in the peripancreatic region. Biopsy of the ulcer was suggestive of moderately differentiated invasive duodenal adenocarcinoma with background of high-grade dysplasia. Due to metastatic malignancy, patient was started on folinic acid, fluorouracil and oxaliplatin without undergoing surgery. Percutaneous biliary drain was placed with resolution of pancreatitis and hyperbilirubinemia. Patient also completed a course of antibiotics due to pseudomonas bacteremia and sepsis secondary to pancreatic phlegmon that was drained. Pain was management with fentanyl patch and oral opioids. Patient was later discharged home with outpatient follow up. Discussion: This case highlights the importance of primary duodenal adenocarcinoma (PDA) which is a very rare malignancy. Its etiology is unknown, however patients with familial adenomatosis polyposis, Peutz-Jeghers syndrome, Crohn’s and celiac disease are at higher risk. Due to non-specific symptoms including anorexia, postprandial fullness, nausea, vomiting, jaundice and abdominal pain, early diagnosis is a challenge for physicians. PDA is most commonly seen in second part of the duodenum with an incidence of 50 -70%. It can be diagnosed with the help of contrast imaging studies along with EGD and biopsy. Management is usually surgical resection with tumors of the second part of the duodenum, proximal and distal infiltrating tumors requiring pancreaticoduodenectomy to ensure radical resection. Lymphovascular invasion, lymph node metastasis and perineural invasion are features associated with poor prognosis and high mortality. For unresectable tumors, palliative surgery or endoscopic treatment is usually indicated.

S3060 Labetalol, a Common Antihypertensive, an Uncommon Cause of Drug-Induced Liver Injury (DILI)

Introduction: Labetalol is an antihypertensive medication (AHM) commonly used as first line agent for non-severe hypertension in pregnancy. We present a case of DILI in a young woman transitioned to labetalol while attempting to conceive. Case Description/Methods: A 35-year-old woman with a h/o hypertension, hashimoto's thyroiditis, anxiety, obesity (BMI 34) was admitted to our hospital for abdominal pain, jaundice, pruritus and aminotransferase (LFT) elevations. She had been admitted previously at an outside facility with nausea, anorexia, and elevated LFTs (ALT 1264, AST 1419, ALP 294, TBili 5) 20 weeks after initiation of labetalol. There were no h/o alcohol abuse or risk factors for hepatitis B/C. Home medications including labetalol were stopped. Imaging studies including MRCP showed no evidence of biliary obstruction. Infectious workup (hepatitis A/B/C/E, CMV, HSV, EBV) and drug/tox screen were negative. A liver biopsy showed acute hepatocellular injury without eosinophils, steatosis, cholestasis or fibrosis; differentials included DILI and infectious hepatitis. LFTs improved, patient was discharged and labetalol restarted. Two weeks later, she presented to our hospital with worsening jaundice. Admission labs: ALT 905, AST 1553, ALP 257, TBili 19.8, INR 1.4 and creatinine 1. On exam, there was no stigmata of chronic liver disease or encephalopathy. Labetalol was discontinued. Infectious, hereditary, metabolic were negative. ANA was positive (1:320) homogenous pattern with mild elevation in IgG. Prednisolone 40 mg daily was started with rapid improvement in LFTs. At 8 week follow up, she was asymptomatic and LFTs were near normal (Tbili 2); prednisolone was tapered. Discussion: Mild to moderate, transient aminotransferase elevations are noted in up to 8% of patients on labetalol. But they are asymptomatic and resolve even with continuation of the medication. Severe liver injury however is rare and rapid resolution typically ensues after cessation of the drug. However acute liver failure, death and OLT have been reported. There are isolated case reports and small case series of labetalol induced DILI, mostly in pregnant women. In a case series, 3 out of 11 patients died and 1 of 5 patients who had liver biopsy had chronic active hepatitis. The mechanism of labetalol hepatic injury is believed to be idiosyncratic. Inadvertent rechallenge has been shown to cause recurrence of DILI. We present this case to increase awareness of labetalol induced DILI as it is the most commonly used AHM in pregnant women.

S3415 Gastroenterological Manifestations in a Patient With Common Variable Immunodeficiency

Introduction: Gastrointestinal manifestation of common variable immunodeficiency (CVID) can present with protein-losing enteropathy (PLE). A wide spectrum of liver injuries can occur with CVID, including nodular regenerative hyperplasia (NRH). Case Description/Methods: 41 y.o. female with PMH of CVID on IgG, chronically elevated LFTs, and nutritional deficiencies. Patient presented with 8-year history of diarrhea, bloating, weight loss, abdominal pain, hepatic encephalopathy (HE), new ascites, and shock. Previously was diagnosed with celiac disease and has strictly followed a gluten-free diet with no improvement. EGD on the current presentation showed visible changes in duodenal mucosa including villous flattening. Biopsies this time revealed villous flattening and absence of plasma cells consistent with CVID enteropathy. Liver biopsy 5 years prior to admission showed no liver disease. Serologic workups, including anti-gp210 and anti-sp100, were negative. Biopsy showed nodular regenerative hyperplasia and non-cirrhotic portal hypertension, which was confirmed by reticulin stain. Patient was started on budesonide 9 mg daily for treatment of PLE, and marked improvement of diarrhea was noted. Non-cirrhotic portal hypertension was managed with furosemide and spironolactone. HE was managed with oral lactulose. The patient was started on enteral and parenteral supplements. Discussion: Duodenal villous atrophy which is a diagnostic criterion for celiac disease can be seen in multiple other conditions including immune disorders such as CVID. In CVID patients with gastrointestinal symptoms, up to 80% of biopsies from different sites in the GI tract will show histological abnormalities. Given their common presentation, celiac disease can be initially diagnosed. The absence of plasma cells and apoptosis presence in duodenal biopsy can suggest PLE diagnosis. Serological studies are not reliable for celiac disease diagnosis due to deficiency of immunoglobulin production in CVID. Steroids can be used for the treatment of PLE in CVID. Hepatic manifestations in CVID are extremely varied and often misdiagnosed given they can mimic other diseases. NRH is a potentially fatal complication of CVID. Recognition of this complication allowed for symptom resolution within two days of starting lactulose therapy. NRH in CVID represents an autoimmune-like liver disease that might be driven by a local vasculopathy, and thus severe cases can warrant a trial of immunosuppression.

S2989 Excessive Hormonal Therapy in a Male Transitioning to a Female Causing Cirrhosis

Introduction: High doses of progestins/estrogens can cause elevated liver enzymes, serum aminotransferase elevations with no changes in alkaline phosphatase or bilirubin, 1 to 2 weeks after treatment. These side effects are usually transient and resolve with dose modification or discontinuation. We present a unique case where a male in-transition to female was found to be cirrhotic from hormonal dose therapy. Gastroenterologists should be aware of the importance of starting hormonal therapy in the transgender process as exogenous estrogen therapy may lead to underlying liver disease. Case Description/Methods: This is a 63 year male on hormone replacement therapy who presented to the hospital for evaluation of hyperlipidemia, hypertension, diabetes, and gender dysmorphia with concerns of questionable abdominal pain and early findings of cirrhosis. During evaluation, he complained of abdominal pain, jaundice, and dark urine. His LFTs were unremarkable prior to the visit. Upon inquiry of a prior history of fatty liver disease, he admitted not following up with his doctor. The patient then described how he had recently begun hormonal therapy to transition to a female. He reported first starting on an estrogen patch with a transition to estradiol 2mg daily. He denied having a prior history of alcohol abuse or other risk factors of cirrhosis. His liver function tests were noted to be T. Bili of 6.3, D. Bili of 3.2, ALK phos of 263, AST of 51, ALT of 176 and lipase of 100. Given his elevated LFTs an ultrasound and MRCP were performed which showed cirrhosis with portal hypertension and cholelithiasis. He did not have any synthetic liver dysfunction. Upon discontinuation of his estradiol his LFTS resolved back to baseline after five days. Discussion: Gastroenterologists should be aware of gender-affirming hormonal therapies in the transgender population as they can lead to long term sequale such as developing cirrhosis. Evidence in the literature is sparse with no consensus on the long term effects of high dose hormone therapy. Further studies should focus on the risk factors of starting hormonal therapy using demographic characteristics, BMI, and alcohol use as further parameters for gauging cirrhosis. We present the case of a 63-old trans-female patient whose hormone therapy can be associated directly with liver cirrhosis.

S3226 Hepatic Sarcoidosis Manifesting as Asymptomatic Elevation in Liver Enzymes

Introduction: Sarcoidosis is a systemic disorder of unknown etiology characterized by the formation of non-caseating granulomas and can affect any organ in the human body. The most frequently involved organs are lungs and hilar lymph nodes; however, involvement of the liver has been described in prior literature. The spectrum of hepatobiliary involvement can range from asymptomatic hepatic granulomas, and minimally deranged LFTs to symptomatic disease complicated with cholestasis, portal HTN, and cirrhosis. We report a case of asymptomatic LFT elevation in a patient with a prior history of sarcoidosis. Case Description/Methods: An 82-year-old African American woman with a past medical history of coronary artery disease, hyperlipidemia, hypertension, Asthma, and Sarcoidosis presented with asymptomatic elevated LFTs discovered by her PCP. The patient denied any complaints from the GI or any other organ system standpoint. Prior blood transfusions, needle sharing, IV drug use, excessive alcohol use, herbal/alternative medicine use, recent changes in medications, or suicidal ideation were ruled out by meticulous history taking. Initial AST, ALT, ALP, GGT, T. bilirubin, and CK measured 783, 532, 1041, 443, 1.6, and 5,699, respectively. (Table 1) Imaging ruled out gallstone and intra-abdominal pathologies, prompting further investigation of possible infiltrative/infectious/autoimmune/neoplastic etiology. Subsequent laboratory findings ruled out thyroid abnormalities, viral or toxic hepatitis, hemochromatosis, Wilson’s Disease, autoimmune hepatitis, and primary biliary cholangitis. The liver biopsy showed granulomatous hepatitis and noncaseating (non-necrotizing) epithelioid granuloma favoring sarcoid deposition (Figure 1). Discussion: This case highlights the importance of considering hepatic sarcoidosis as a potential cause of LFT elevation, especially in a patient with a prior history of sarcoidosis. In such patients, after common causes of LFT elevations have been ruled out based on the patient’s history, imaging, blood tests, and screening for autoimmune diseases, liver biopsy should be considered earlier in the management course to reach a timely diagnosis. This is especially important as not all cases of hepatic sarcoidosis require treatment, so considerations for treatment vs. closer follow-up could be decided as soon as the liver biopsy results are available. This would significantly decrease the burden on healthcare resources by avoiding unnecessary testing and aiding in timely and accurate management.Figure 1.: Liver Biopsy Results. Table 1. - LFT trend Test name Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day of discharge AST 783 673 566 469 429 355 267 237 ALT 532 441 395 335 330 284 238 224 ALP 1041 920 898 822 780 715 631 653 Total Bilirubin 1.6 1.5 1.3 1.0 0.9 0.9 0.9 1.0 CK 5699 4154 3225 2721 2378 1402 725 437

S1724 Eosinophilic Cholangitis: A Great Mimic

Introduction: Eosinophilic Cholangitis (EC) is a rare infiltrative disorder of the biliary tree and a diagnostic dilemma. The initial presentation mimics malignancy and is distinguished by histopathology. Steroid response supports the diagnosis. This case elucidates the diagnostic and therapeutic approach to EC in a patient with acute jaundice. Case Description/Methods: A 44-year-old female with a history of SLE and marginal cell lymphoma in remission presented with fevers, leukocytosis, abdominal pain, and hyperbilirubinemia. She underwent an ERCP that showed a common bile duct (CBD) stricture with stent placement that was removed 6 weeks later (Figure). She then underwent a cholecystectomy for chronic cholecystitis with an intraoperative liver biopsy for persistently elevated LFTs (AST 512 U/L, ALT 500 U/L). Surgical specimens showed dense eosinophils at the cystic duct margin with mild non-specific lobular inflammation involving 15% of liver parenchyma. Six months later, she presented to our hospital with worsening abdominal pain and jaundice. Pertinent labs included a total bilirubin of 16.9 mg/dL, AST 321 U/L, ALT 335 U/L, and alkaline phosphatase 2700 U/L. MRCP showed CBD narrowing at the hilum with intrahepatic ductal dilation She underwent an ERCP which identified a Bismuth IV hilar stricture and a ductal polypoid mass on cholangioscopy. Two biliary stents were placed across the stricture into the right and left intrahepatic ducts. A direct biopsy, while negative for malignancy, revealed marked eosinophilia. Labs included peripheral eosinophilia of 0.78 x109/L. IgG4 and Anti-mitochondrial antibody were normal. A month later, repeat ERCP with stents exchange and ductal mass re-biopsy was performed given high concern for malignancy, however again demonstrated sheets of eosinophils. After multidisciplinary discussion, she was presumptively diagnosed with EC and started on 40mg of prednisone. Seven weeks later, repeat ERCP showed complete resolution of the stricture. LFTs and bilirubin normalized. Her symptoms resolved and she was transitioned to azathioprine for maintenance. Discussion: EC is a rare, benign process affecting the biliary system and poses a significant diagnostic challenge. Our case supports proposed diagnostic criteria for EC, including biliary stricture, eosinophilic infiltration on histopathology, and steroid responsiveness. Our case is unique in our demonstration of the direct cholangioscopy view of this benign entity and the utility of cholangioscopy in achieving the diagnosis.Figure 1.: a) Ductal polypoid mass near common hepatic duct identified via endoscopic retrograde cholangiopancreatography with cholangioscopy. b) Intrahepatic biliary ductal dilatation seen on magnetic resonance cholangiopancreatography. c) Occlusion cholangiogram during endoscopic retrograde cholangiopancreatography showing a Bismuth Type IV common bile duct stricture. d) Occlusion cholangiogram during endoscopic retrograde cholangiopancreatography showing resolution of the common bile duct stricture after steroid treatment. e) Biliary stricture biopsies showing fragments of bile duct mucosa with acute and chronic inflammation with marked eosinophilia. f) Ductal mass/biliary stricture biopsy demonstrating inflammation and eosinophilia on Hematoxylin-eosin stain.

Tazemetostat in patients with tumors with alterations in EZH2 or the SWI/SNF complex: Results from NCI-COG Pediatric MATCH trial Arm C (APEC1621C).

10009 Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients, age 1-21 years, with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms based on genetic alterations detected in their tumor. Arm C evaluated the EZH2 inhibitor tazemetostat in patients whose tumors harbored EZH2 hotspot mutations or SMARCB1 or SMARCA4 loss by immunohistochemistry. Methods: Tazemetostat 1200 mg/m2/dose PO BID was administered to the first 13 patients; after study amendment due to second malignancy noted in the pediatric phase 1 trial, the dose for patients with non-CNS tumors was reduced to 520 mg/m2/dose PO BID. Patients were treated for 28-day cycles until PD or intolerable toxicity (max 26 cycles); response assessments occurred every 2-3 cycles. Primary and secondary endpoints were ORR and PFS, respectively. Results: Twenty eligible and evaluable patients (median age 5 years; range 1-21) were enrolled between Nov 2017 and Sept 2020. SMARCB1 loss was detected in 16/20 (80%) tumors: atypical teratoid rhabdoid tumor (ATRT, n = 8), malignant rhabdoid tumor (MRT, n = 4), epithelioid sarcoma (ES, n = 2), renal medullary carcinoma (RMC, n = 1) and hepatocellular carcinoma (HCC, n = 1). EZH2 mutations were identified in 3/20 (15%) tumors: Ewing sarcoma (n = 2), ependymoma (n = 1). One patient with Langerhans cell histiocytosis (LCH) had SMARCA4 loss. Centrally reviewed, one objective response (PR) was observed (LCH [SMARCA4], 26 cycles at 1200 mg/m2/dose BID). Five other patients had a best response of stable disease (ES [SMARCB1], 26 cycles, 520 mg/m2/dose BID; ATRT [SMARCB1], 13 cycles,1200 mg/m2/dose BID; RMC [SMARCB1], 12 cycles, 520 mg/m2/dose BID; ES [SMARCB1], 9 cycles,1200 mg/m2/dose BID; ATRT [SMARCB1], 6 cycles, 1200 mg/m2/dose BID). No other patients received &gt; 2 cycles. Six-month PFS was 35% (95% CI 15.7%, 55.2%); OS was 45% (95% CI 23.1%, 64.7%). Treatment-related adverse events were consistent with AEs previously reported with tazemetostat, including anemia, thrombocytopenia, elevated LFTs, abdominal pain, dyspnea, infection, and intracranial hemorrhage. Three patients had bromide elevations. Conclusions: In this cohort of children with relapsed tumors harboring EZH2 mutations or loss of SMARCB1 or SMARCA4, tazemetostat did not produce significant objective responses (ORR: 5%, 90% CI 1%, 20%). However, we observed prolonged stable disease of &gt; 6 months (range: 6-26 cycles) in 33% of patients across different histologic diagnoses, including two patients who received the full two years of study therapysuggesting a potential effect of tazemetostat on disease stabilization. Future studies will incorporate tazemetostat in combination with chemotherapy or immunologic agents for patients with these aggressive and difficult to treat tumors. Clinical trial information: NCT03213665.

282 Audit for the Management of Acute Gallstone Disease

Abstract Aim The aim of this audit was to investigate how patients referred by the Emergency Department (ED) with biliary disease were managed. Also, to identify a cohort of patients which could be safely discharged from ED with an outpatient US and follow up with the Surgical Assessment Unit. Method Data was collected from 23/11/20 to 11/12/20. The inclusion criteria were patients referred by ED with abdominal pain and a diagnosis of biliary disease. Data collected included blood results, US results and if they underwent a laparoscopic cholecystectomy (LC). Results There were 22 patients identified; 5 had biliary colic, 4 had cholangitis and 13 had cholecystitis. The 5 patients with biliary colic had almost completely normal bloods on admission. While 16/17 patients with cholecystitis/cholangitis had elevated FBC, CRP or LFTs. US was performed on 3 patients with biliary colic within 3 days of ED attendance. US was performed on 16/17 patients with cholecystitis/cholangitis, mainly within 2 days. None of the patients with biliary colic received antibiotics and 2 had an inpatient LC. All patients with cholecystitis and cholangitis were admitted and treated with antibiotics. 1 patient with cholecystitis had a LC and 7 were on the waiting list. Conclusions This has shown that patients are being imaged with US efficiently and are treated appropriately with antibiotics. It has demonstrated that a blood test in ED is effective at differentiating between biliary colic and other diseases that require admission. However, improvements need to be made to increase access for patients to undergo timely LCs.

Safety and efficacy of combining genotype-guided irinotecan (Iri) with 5FU, leucovorin (LV), oxaliplatin (Ox), and docetaxel (Tax) (gFOLFOXIRITAX): The I-FLOAT phase 1 dose-escalation study for advanced upper GI cancers.

316 Background: 5FU, Ox, Iri, and Tax are each active in upper GI cancers. Triplet cytotoxic therapies (txs) improved survival compared to doublets/singlets. However, combination of all 4 agents (FOLFOXIRITAX) has not been studied. UGT1A1 polymorphisms reduce UGT enzymatic activity predisposing to Iri toxicity. We sought to determine the maximum tolerated dose (MTD) in the 1st month of tx among each of the low (L), intermediate (I) and high (H) risk UGT1A1 genotype (UGT) groups. Methods: Previously untx’d advanced upper GI cancer patients (pts) with ECOG PS 0/1 received gFOLFOXIRITAX (+ trastuzumab if HER2+) with pegfilgrastim. 5FU 2400mg/m2 over 46 hrs, LV 400mg/m2, Ox 85mg/m2, and Tax 25mg/m2 were given IV Q14 days. UGT-L, I, and H risk groups received starting Iri dose levels (DL1) of 120, 105 and 45mg/m2, respectively; Iri doses were escalated in each UGT group by 15mg/m2 increments and Tax to DL2 of 37.5mg/m2 using a I3+3 novel design (Liu &amp; Ji. J Biopharm Stat 2020). Other endpoints included overall safety (thru up to 8 cycles before maintenance 5FU +/- Iri/tras), ORR (RECIST1.1), &amp; ctDNA response (&gt; 50% decrease in highest MAF) by G360 (Guardant Health). Results: From 6/30/2020-8/6/2021 20 pts (8F, 12M) enrolled: median age 50 (range 21-76); 8 ECOG PS 1, UGT-L:I:H with 3:14:3 pts; 10 esophageal, 6 gastric, 2 pancreatic, 1 unknown GI primary and 1 bile duct cancer; 2 pts HER2+; 18 metastatic, 2 locally advanced unresectable. The median (range) of albumin and neutrophil-to-lymphocyte ratio (NLR) were 3.9 mg/dL (3.3-4.6) and 4.28 (1.89-27.6), respectively; 80% (16/20) of pts had a NLR &gt; 2.88, a poor prognostic marker. Dose limiting toxicities (DLTs) were seen in 4 pts: one G3 diarrhea (UGT-H, DL1/DL1 Iri/Tax), two G3 sepsis not neutropenic (one UGT-I, DL2/DL2 Iri/Tax; and one UGT-I, DL3/DL1 Iri/Tax) and one G3 fatigue (UGT-I DL2/DL2 Iri/Tax). MTD has not been reached in any UGT TAX DL1 cohorts to date; currently enrolling UGT-H Iri/Tax DL1/DL1, UGT-I DL4/DL1, &amp; UGT-L DL3/DL1. Any Gr tx related toxicities in ³ 10% pts thru up to 8 cycles: nausea (70%), fatigue (70%, 5% G3), diarrhea (65%, 5% G3), anorexia (50%), peripheral neuropathy (30%, 5% G3), anemia (30%), thrombocytopenia (25%), elevated LFTs (25%), hyponatremia (25%), vomiting (20%), mucositis (20%, 5% G3), hyperglycemia (20%), edema (15%), alopecia (15%), hypocalcemia (15%) and dysgeusia (10%). Of evaluable pts across all cohorts, PR/CR was seen in 13/16 (81%) patients, with 2 (12.5%) SD and 1 (6.25%) PD for a disease control rate of 94%. Of evaluable pts, best ctDNA response was seen in 12/13 (92%). Conclusions: gFOLFOXIRITAX demonstrated tolerability at initial dose levels of Iri/Tax, with dose escalation continuing. Efficacy is promising and could be an aggressive approach in upper GI cancers having high relapse risk in curative-intent settings. Clinical trial information: NCT04361708.

Reasons for Discontinuation of Dantrolene in Persons with Brain Injuries with Spasticity: A Retrospective Review

Dantrolene is a muscle relaxant used to treat spasticity in persons with neurological injuries. At our acute rehabilitation unit, there have been anecdotal reports of patients developing dysphagia after starting dantrolene. The objective of this study is to investigate association between dantrolene and dysphagia in addition to other side effects of dantrolene. A retrospective chart review was performed on patients 18 years old or older that were started on dantrolene for spasticity during their acute rehabilitation admission. Exclusion criteria included any patients that have missing data, were started on dantrolene for reasons other than spasticity, or were started on dantrolene outside of their inpatient admission. Between 2015-2018, 62 out of 1,542 inpatients were started on dantrolene. Fifty patients tolerated the medication, and 12 patients discontinued the medication due to dysphagia (n=2), fatigue (n=3), elevated LFTs (n=1), lack of effect (n=3), and other complications (n=3). Demographic comparisons and regression models revealed no significant predictors of dysphagia and other side effects. Relatively high percentage of patients (19.4%) who were started on dantrolene discontinued the medication due to side effects or lack of efficacy. These findings can provide clinicians with insight into expected side effects when using dantrolene to treat spasticity.

S1668 Pancreaticoportal Vein Fistula: A Very Rare Complication of Pancreatitis

Introduction: Pancreatic pseudocyst formation is a well-known complication of pancreatitis. Fistualization between a pancreatic pseudocyst and the portal system is a very rare complication of pancreatitis. Presentation varies from vague abdominal pain and elevated LFTs to systemic lipolysis, septic shock and death. It carries a high mortality risk if not identified promptly and managed. Case Description/Methods: 52-year-old male with a history of lymphoma s/p chemotherapy and splenectomy and HTN presented with 3 days of abdominal pain, decreased PO intake, and bilious emesis. He drinks half a bottle of vodka daily. His labs were notable for a significantly elevated lipase, lactic acidosis, severe AKI and elevated LFTs. CT abdomen was performed which was consistent with acute pancreatitis. He was admitted and treated conservatively. RUQ US revealed no gallstones. Pancreatitis was likely secondary to alcohol use. During this hospitalization he developed leukocytosis, fever, and worsening nausea and pain. An MRCP was obtained which revealed acute pancreatitis without definite focal pancreatic lesion, no cholelithiasis or choledocholithiasis. An MRI abdomen with contrast was obtained which revealed acute pancreatitis with necrosis in the pancreatic neck. There was no discrete abscess identified. He did not require surgical intervention. His course was complicated by C. difficile which was treated with oral vancomycin. The patient clinically improved and was discharged in stable condition after 11 days. About 1 month later the patient again presented with abdominal pain and "bulging" of his stomach. A CT and MRI of the abdomen revealed a massive pancreatic pseudocyst with communication with the porta hepatis. He was started on broad spectrum IV antibiotics and underwent a robotic cystgastrostomy. It was noted the pseudocyst was mostly fluid filled with small necroma component. Intraoperative cultures of the necroma remained without growth. The remainder of his hospital course was complicated by fever, leukocytosis and a pleural effusion with LLL collapse. The effusion was drained via chest tube. Pleural fluid cultures were negative. He was discharged in stable condition on IV antibiotics. Discussion: PPVF carries a high mortality risk and should be identified promptly. MRI/MRCP and ERCP aid in the diagnosis of PPVF. Treatment options include supportive medical management, surgical or endoscopic drainage of pseudocysts, fistula embolization, or partial pancreatectomy.Figure 1.: Multiloculated pseudocyst with fingerlike extensions into the porta hepatis.

S2694 Severe Acute Liver Failure in a Patient With SARS-CoV-2 Infection

Introduction: Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, are regularly found to have elevated LFTs. Up to 46% had elevated AST and 35% had elevated ALT. Occasional elevations in GGT, ALP, and total bilirubin are also seen. These elevations were usually below 5 times the upper limit of normal (ULN). Less than 10% of patients had severe liver injury (ALT > 5 times ULN). Hepatic injury in COVID-19 can be attributed to numerous causes including direct injury, drug toxicity and inflammatory storm. Direct injury is thought to occur when SARS-CoV-2 binds directly to ACE-2 which are abundantly expressed in biliary and liver epithelial cells. We present the case of an 88-year-old COVID-19 patient with severe liver failure managed conservatively. Case Description/Methods: 88-year-old male with history of CHF, atrial fibrillation on Apixaban, DM-2, HTN and recent diagnosis of COVID-19 presented with shortness of breath. Vitally, he was normotensive but hypoxic. Initial labs are shown in Table 1. He denied an established history of liver disease, alcohol use or hepatotoxic drug use. Chest CTA had findings concerning for COVID-19 pneumonia and acute pulmonary embolism. He was not started on Remdesivir due to elevated LFTs. His acute hepatitis panel and acetaminophen level were negative. The patient’s LFTs continued to worsen over his hospital course (Image 1). Transfer to a tertiary liver center was not considered due to his tenuous condition, age, and comorbidities. On day five the patient’s AST and ALT started trending down. However, total bilirubin continued to rise, and ALP stayed relatively stable. His respiratory status continued to worsen, and he was eventually transitioned to comfort care. Discussion: In the absence of an established history of liver disease, alcohol abuse, or hepatotoxic drug use, we believe that our patient’s acute liver failure might have been a direct complication of COVID-19 infection. Treatment with 1-2 drugs from the following categories: hepatoprotective, anti-inflammatory, and jaundice-reducing agents including polyene phosphatidyl choline, glycyrrhizic acid, bicyclol, and vitamin E has been proposed to reduce the burden of liver injury. With the increasing number of cases of liver injury with COVID-19, it is pivotal to identify its pathogenesis, acute interventions, and potential long-term complication to treat this life-threatening condition promptly and effectively.Table 1.: demonstrating our patient’s initial labs.Figure 1.: Image 1 demonstrating lab trend of our patient over his hospital stay.